N-tert-butoxycarbonyl-methylenedioxymethamphetamine, an methylenedioxymethamphetamine derivative, exhibits rewarding and reinforcing effects by increasing dopamine levels.

An N-protected methylenedioxymethamphetamine (MDMA), N-tert-butoxycarbonyl-3,4-methylenedioxymethamphetamine (t-BOC-3,4-MDMA), contains tert-butoxycarbonyl and can remain undetected in the illicit drug market. It is a new type of precursor substance that is not a chemical intermediate and can be converted into a controlled substance, MDMA, by deprotection of the N-tert-butoxycarbonyl group. Categorization of this chemical into a precursor or psychotropic substance is an issue because it is an unprecedented precursor that could have misuse potential.

Discriminative stimulus and reinforcing effects of diclazepam in rodents.

Diclazepam, a designer benzodiazepine, is a lesser-known novel anxiolytic substance and a structural analog of diazepam. Although several case studies have reported the adverse effects of diclazepam, their potential impacts remain unknown. Therefore, this study aimed to determine the effects of diclazepam in rodents using drug discrimination, locomotor activity, self-administration (SA), and conditioned place preference (CPP) tests.

Withdrawal from 3-Fluoroethamphetamine induces hyperactivity and depression-like behaviors in male mice.

3-Fluoroethamphetamine (3-FEA) belongs to the amphetamine class of stimulant drugs and functions as a releasing agent for the monoamine neurotransmitters norepinephrine, dopamine, and serotonin. 3-FEA acts on the central nervous system and elicits physical and mental side effects, such as euphoria, increased heart rate, and excitement. However, little is known about the withdrawal symptoms and behavioral changes induced by 3-FEA administration.

New multiple cardiac ion channel screening system for preclinical Torsades de Pointes risk prediction under the Comprehensive Proarrhythmia Assay concepta.

Cardiotoxicity, particularly drug-induced Torsades de Pointes (TdP), is a concern in drug safety assessment. The recent establishment of human induced pluripotent stem cell-derived cardiomyocytes (human iPSC-CMs) has become an attractive human-based platform for predicting cardiotoxicity. Moreover, electrophysiological assessment of multiple cardiac ion channel blocks is emerging as an important parameter to recapitulate proarrhythmic cardiotoxicity.

Rewarding and Reinforcing Effects of 25H-NBOMe in Rodents.

The drug 25H-NBOMe is a new psychoactive substance (NPS). The use of these substances is likely to pose a threat to public health because they elicit effects similar to those of known psychoactive substances with similar chemical structures. However, data regarding the abuse potential of 25H-NBOMe are lacking.

Neurotoxic and cardiotoxic effects of -methyl-1-(naphthalen-2-yl)propan-2-amine (methamnetamine) and 1-phenyl-2-pyrrolidinylpentane (prolintane).

Two synthetic phenylethylamines, N-methyl-1-(naphthalen-2-yl)propan-2-amine (MNA) and 1-phenyl-2-pyrrolidinylpentane (prolintane), are being abused by people seeking hallucinogens for pleasure. These new psychotropic substances may provoke problems because there is no existing information about their toxicity and pharmacological behaviors. Therefore, we evaluated the safety of nerves and cardiovascular systems by determining toxicity after MNA and prolintane drugs administrations to mice and rat.

Rewarding and reinforcing effects of two dissociative-based new psychoactive substances, deschloroketamine and diphenidine, in mice.

Dissociative-based new psychoactive substances (NPSs) are increasingly available through the Internet, and public health problems related to the recreational use of these substances have been increasing globally. Two such NPSs are deschloroketamine and diphenidine, which are primarily used recreationally as ketamine substitutes. However, there is little scientific evidence to describe the dependence liability of NPSs.

The abuse potential of prolintane in rodents: Behavioral pharmacology approaches.

Prolintane (1-Phenyl-2-pyrrolidinylpentane), a synthetic central nervous system (CNS) stimulant, is structurally similar to amphetamine but pharmacologically acts as a dopamine reuptake inhibitor like cocaine. While several case studies reported adverse effects and recreational use of prolintane, the abuse potential of the drug has not been systemically examined yet. In the present study, we evaluated the behavioral effects of prolintane regarding its abuse liability in rodents using locomotor activity, conditioned place preference (CPP), self-administration (SA), and drug discrimination paradigms, as well as in-vivo microdialysis experiment.

2-((2-(4-Iodo-2,5-dimethoxyphenyl)ethylamino)methyl)phenol (25I-NBOH) and 2-(((2-(4-chloro-2,5-dimethoxyphenyl)ethyl)amino)methyl)phenol (25C-NBOH) induce adverse effects on the cardiovascular system.

Two new psychoactive substances (NPSs) classified as phenethylamines, namely 2-((2-(4-Iodo-2,5-dimethoxyphenyl)ethylamino)methyl)phenol (25I-NBOH) and 2-(((2-(4-chloro-2,5-dimethoxyphenyl)ethyl)amino)methyl)phenol (25C-NBOH), are being abused by people seeking recreational hallucinogens. These NPSs may cause serious health problems as their adverse effects are not known in most cases. Therefore, in the present study, we evaluated the cardiotoxicity of 25I-NBOH and 25C-NBOH using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, rat electrocardiography (ECG), Langendorff test, and human ether-a-go-go-related gene (hERG) assay.

Characterization of in vitro phase I metabolites of methamnetamine in human liver microsomes by liquid chromatography-quadrupole time-of-flight mass spectrometry.

N-Methyl-1-(naphthalen-2-yl)propan-2-amine (methamnetamine, PAL-1046) is an amphetamine-based new psychoactive substance (NPS). Methamnetamine has been reported to cause excessive release of serotonin, and it is classified as an empathogen or entactogen. It is not regulated as a controlled substance in most countries, and there are no studies on its metabolism.

Development and validation of dual-cardiotoxicity evaluation method based on analysis of field potential and contractile force of human iPSC-derived cardiomyocytes / multielectrode assay platform.

A recent in vitro cardiovascular safety pharmacology test uses cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) to overcome the limitations of the classical test systems, such as species differences and local channel analysis. The Comprehensive in vitro Proarrhythmia Assay (CiPA) is a new proarrhythmia screening paradigm proposed by a CiPA steering expert group, which essentially requires iPSCs derived cardiomyocyte-based electrophysiological evaluation technology. Moreover, the measurement of the contractile force is also emerging as an important parameter to recapitulate non-proarrhythmic cardiotoxicity.

Simple determination of azasetron in rat plasma by column-switching high-performance liquid chromatography.

For the quantification of azasetron in rat plasma samples, a column-switching HPLC method was developed and validated. Following dilution of plasma samples with mobile phase A (17 mM potassium phosphate buffer (pH 3.0)) and simple protein precipitation by addition of perchloric acid (60%), the mixture was directly injected onto the pre-column.

High-performance liquid chromatography assay for the determination of the HIV-protease inhibitor tipranavir in human plasma in combination with nine other antiretroviral medications.

An accurate, sensitive and simple reverse-phase (RP) high-performance liquid chromatography (HPLC) assay has been developed and validated for the simultaneous quantitative determination of tipranavir with nine other antiretroviral drugs in plasma. A liquid-liquid extraction of the drugs in tert-butylmethylether (TBME) from 200 microL of plasma is followed by a reversed phase gradient HPLC assay with UV detection at 210 nm. The standard curve for the drug was linear in the range of 80-80,000 ng/mL for tipranavir; 10-10,000 ng/mL for nevirapine, indinavir, efavirenz, and saquinavir; and 25-10,000 ng/mL for amprenavir, atazanavir, ritonavir, lopinavir, and nelfinavir.

Column-switching high-performance liquid chromatographic analysis of fluvastatin in rat plasma by direct injection.

A column-switching high-performance liquid chromatographic (HPLC) method has been developed and validated for quantification of fluvastatin in rat plasma. Plasma samples were diluted with an equal volume of mobile phase, i.e.

The effects of food on the bioavailability of fenofibrate administered orally in healthy volunteers via sustained-release capsule.

Objective: To examine the effects of food on plasma concentration and bioavailability of fenofibrate administered as a sustained-release capsule.

Methods: Twenty-four healthy Korean volunteers were enrolled in a randomised, open-label, balanced, three-treatment, three-period, three-sequence, single oral dose, crossover pharmacokinetic study. A single dose of fenofibrate (250 mg sustained-release capsule) was administered on three occasions -- after overnight fasting, after consumption of a standard breakfast and after a high-fat breakfast.

Prediction of the permeability of drugs through study on quantitative structure-permeability relationship.

This study is to research the quantitative structure-permeability relationship of 20 drugs having similar structure. Permeability was determined by using the Caco-2 cell in vitro model. The apparent permeability coefficient (Papp) of each drug both of apical to basolateral side and basolateral to apical side was measured at the concentration corresponding to 0.

Column-switching high-performance liquid chromatographic method for the determination of zaltoprofen in rat plasma.

A direct injection column-switching high-performance liquid chromatography (HPLC) method was developed and validated for quantification of zaltoprofen in rat plasma. Following dilution with mobile phase A, i.e.

Prediction on the chiral behaviors of drugs with amine moiety on the chiral cellobiohydrolase stationary phase using a partial least square method.

Quantitative Structure-Resolution Relationship (QSRR) using the Comparative Molecular Field Analysis (CoMFA) software was applied to predict the chromatographic behaviors of chiral drugs with an amine moiety on the chiral cellobiohydrolase (CBH) columns. As a result of the Quantitative CoMFA-Resolution Relationship study, using the partial least square method, prediction of the behavior of drugs with amine moiety upon chiral separation became possible from their three dimensional molecular structures. When a mixed mobile phase of 10 mM aqueous phosphate buffer (pH 7.

Determination of phloroglucinol in human plasma by high-performance liquid chromatography-mass spectrometry.

A sensitive and selective liquid chromatographic method coupled with mass spectrometry (LC-MS) was developed for the quantification of phloroglucinol in human plasma. Resorcinol was used as internal standard, with plasma samples extracted using ethyl acetate. A centrifuged upper layer was then evaporated and reconstituted with mobile phase.